# Combined Impact of Smoking Duration and Malnutrition on Cancer Survival: Insights Into Systemic Inflammation

## TL;DR

This study shows that both smoking and malnutrition worsen cancer survival, with their combined effect being especially harmful due to increased inflammation.

## Contribution

The study reveals a dose-response relationship between smoking duration and malnutrition on cancer mortality and links it to systemic inflammation.

## Key findings

- Smoking and malnutrition independently increase cancer mortality risk, with the highest risk in patients with both factors.
- Prolonged smoking and worsening malnutrition are associated with elevated levels of inflammatory markers like CRP and WBC.
- Every additional 5 years of smoking increases mortality risk by 6%, and 10 years of smoking increases it by 86% in malnourished patients.

## Abstract

Smoking and malnutrition are established risk factors for cancer survival, yet evidence on their combined effects remains limited. This study aimed to investigate the joint impact of smoking duration and malnutrition on overall survival (OS) in patients with solid tumours and to explore the potential underlying mechanism—systemic inflammation.

This study was based on the Investigation of Nutrition Status and Clinical Outcomes in Common Cancers (INSCOC), which enrolled 29 988 patients with solid tumours and collected data on smoking status, nutritional status assessed by the Patient‐Generated Subjective Global Assessment (PG‐SGA) and haematological indicators. Restricted cubic spline regression, Cox proportional hazards models and logistic regression were used to examine the associations of smoking and malnutrition with OS and their relationships with inflammatory markers.

A total of 29 988 patients were included, among whom 7649 were smokers with malnutrition (male: 7095 [92.8%]; female: 554 [7.2%]); their mean age was 60.17 ± 10.57 years. Both smoking and malnutrition independently increased mortality risk in patients with solid tumours (HR = 1.24, 95% CI 1.15–1.35, p < 0.001; HR = 1.25, 95% CI 1.17–1.33, p < 0.001), with the highest risk observed in those with both risk factors (HR = 1.46, 95% CI 1.36–1.57, p < 0.001). Smoking duration showed a dose–response association with OS. Specifically, among smokers, every additional 5 years of smoking increased the risk of death by 6% (HR = 1.06, 95% CI 1.04–1.07, p < 0.001). In patients with malnutrition, every additional 10 years of smoking increased the risk of death by 86% (HR = 1.86, 95% CI 1.55–2.23, p < 0.001). Further analyses showed that, with increasing smoking duration, CRP increased from 3.50 [1.79, 13.60] to 6.00 [2.87, 24.90] mg/L and WBC from 5.70 [4.47, 7.31] to 6.47 [5.10, 8.40] × 109/L (both p < 0.001). With worsening malnutrition, CRP rose from 3.11 [1.23, 6.28] to 10.00 [3.20, 40.70] mg/L and WBC from 5.70 [4.51, 7.24] to 6.39 [4.84, 8.71] × 109/L (both p < 0.001), indicating that prolonged smoking and aggravated malnutrition were associated with elevated systemic inflammation.

Smoking and malnutrition are crucial prognostic factors for survival in cancer patients. The results emphasize the critical role of managing smoking duration and improving nutritional status in the care of cancer patients. Clinically, attention should be given to controlling inflammation levels in patients with smoking and malnutrition.